..The observed SAR is in agreement with established pharmacophore models for 5-HT₃ ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches...

Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain

..We compare the pharmacological profiles of a new histamine H4 receptor agonist 2-(2-guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H4 receptor agonist, 4-methylhistamine...

..Our ligand-steered, experimentally supported protein modeling method gives new insights into ligand recognition by H(4)R and can be used as a general approach to elucidate the structure of protein-ligand complexes...

..Altogether, in this study, we show overlapping, yet different binding sites for two high-affinity CXCR3 antagonists, which offer new opportunities for the structure-based design of allosteric modulators for CXCR3. ..

..Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H 3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research...

Small and colorful stones make beautiful mosaics: fragment-based chemogenomics

..The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes...

A novel series of histamine H4 receptor antagonists based on the pyrido[3,2-d]pyrimidine scaffold: comparison of hERG binding and target residence time with PF-3893787

..On the basis of the derived structure-activity relationships and additional pharmacological results, a pharmacophore model was constructed, which will be the premise for the design of novel H4R ligands...

..These novel inverse agonists serve as valuable tools to elucidate the role of constitutive signaling in the pathogenesis of viral infection and may have therapeutic potential as leads for new antiviral drugs...

..In this review, we describe the receptor protein, its putative role in (patho)physiology and the latest ligands that are being developed to explore the feasibility of the H(4) receptor as a drug target...

Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors

..These results point to an important role of the second extracellular loop in the agonist binding to the H(4) receptor and provide a molecular explanation for the species difference between human and mouse H(4) receptors...

..One of the compounds, AMG487, progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy. New antagonist classes are being developed to reveal the full therapeutic potential of CXCR3...

Synthesis and structure-activity relationships of 3H-quinazolin-4-ones and 3H-pyrido[2,3-d]pyrimidin-4-ones as CXCR3 receptor antagonists

..The analysis of the dual binding mode of these dibenzosuberyl-containing compounds can lead to better understanding of the complex mode of action of similar tricyclic ligands on Cys-loop receptors...

Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28

..These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection...

..These studies provide a molecular understanding for the action of a variety of H 4 receptor-ligands. The resulting H 4 receptor model will be the basis for the development of new H 4 receptor-ligands...

Exploring a pocket for polycycloaliphatic groups in the CXCR3 receptor with the aid of a modular synthetic strategy

..A CXCR3 pocket capable of accommodating polycycloaliphatics was explored using a modular synthetic strategy. The systematic studies reveal that the tricyclic 2-adamantane and bicyclic (iso)bornyl group are efficiently recognized by CXCR3...

..The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H(3) and H(4) receptors and exhibit pK(i) values up to 7.5 at the human H(4)R...

Several down, a few to go: histamine H3 receptor ligands making the final push towards the market?